The nitric oxide donor pentaerythritol tetranitrate lowers hypertension and angiogenic imbalance in pregnancies with impaired uterine perfusion—a secondary analysis of a randomized trial

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Objective: A multicenter, randomized controlled trial investigated the effects of the nitric oxide donor pentaerythritol tetranitrate (PETN) in pregnant women with impaired uterine perfusion.1 PETN did not significantly reduce the composite primary outcome of fetal growth restriction (FGR) or perinatal death, but it led to significant reductions of 55% in pregnancy-induced hypertension (PIH) and of 27% in preterm birth. Participants in the PETN group were less likely to be admitted to the hospital during pregnancy (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.30–0.85; P=.01).1 A dysfunctional placenta releases anti-angiogenic factors, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), while suppressing pro-angiogenic factors, like placental growth factor (PlGF). This imbalance disrupts endothelial function and vascular health and leads to hypertension and impaired placental perfusion. This secondary analysis focuses on the effect of PETN on maternal outcomes and angiogenic profiles. Study Design: Pregnant women who presented with a mean uterine artery pulsatility index of >95th percentile at 19+0 to 22+6 weeks of gestation were randomized to receive 50 mg PETN or placebo twice daily. The maternal data that were collected upon inclusion, at study visits every 4 weeks, and at delivery included blood pressure, adverse events, serum sample sFlt-1/PlGF ratios, and preeclampsia-related serum parameters. Residual samples were obtained on availability and were used to determine the sEng and PETN metabolite serum concentration. The intent-to-treat principle was used, and continuous outcomes were compared using the Mann-Whitney U test and categorical outcomes were compared using Fisher’s exact test. Results: Of the 317 women who were enrolled in the study, clinical data were available for further analyses for 307 women. The sFlt-1/PlGF ratio values were available for 290 participants. Residual samples for the determination of sEng and PETN metabolite concentrations were available for 100 participants (46 PETN cohort and 55 placebo group). There were no differences noted between the 2 study groups, including in the sFlt-1/PlGF ratio values (Supplemental Table 1). The incidence of PIH was significantly reduced in the PETN group (23.9%; 37/155 women) when compared with the placebo group (36.6%; 59/161 women) (Table). Preeclampsia, defined as PIH and at least 1 additional feature, such as FGR, liver enzyme alteration, kidney malfunction, or hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, was observed in 20% (31/155 women) of the PETN group and in 29.2% (47/161 women) of the placebo group (P=.07). The mean of the maximum reported systolic blood pressure was significantly lower in the PETN group when compared with the placebo group (130 mm Hg vs 135 mm Hg; P=.019), and the proportion of participants whose blood pressure values remained <140 mm Hg systolic and/or <90 mm Hg diastolic was higher in the PETN group (HR, 0.6; CI, 0.397–0.906; P=.013) (Supplemental Figure).

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.